Effects of Single Exposures to Antiproliferative Agents on Ocular Fibroblast-mediated Collagen Contraction

Purpose: To determine the effects of short-duration treatments with 5-fluorouracil (5FU) and mitomycin-c (MMC) on "activated" and "nonactivated" ocular fibroblasts in collagen lattices.

Methods: Activated and nonactivated ocular fibroblasts seeded in collagen lattices were exposed to single 5-minute treatments with 5FU (0.01 to 25 mg/ml) and MMC (0.01 to 1 mg/ml). The effects of these treatments on lattice contraction, cellularity, cellular viability, cellular structure, and actin distribution were investigated.

Results: Treatment with 5FU (0.01 to 25 mg/ml) or MMC (0.1 to 1 mg/ml) significantly inhibited (P < 0.001 and P < 0.0001, respectively) lattice contraction compared to water controls. The degree of inhibition was greater in lattices containing nonactivated cells than in those containing activated cells. Activated cell viability and cellularity, unlike their nonactivated counterparts, were not significantly affected (P > 0.0083) by treatment with 5FU at high concentrations (25 mg/ml). MMC treatment had significant effects on cell viability and cellularity (P < 0.0001). Treatment with 5FU and MMC also affected cellular structure and actin distribution compared to water controls.

Conclusions: Single, short exposures to 5FU or MMC inhibit ocular fibroblast-mediated collagen contraction. MMC causes cell death and a decrease in cellularity at high concentrations. The results also indicate that collagen lattices seeded with activated and nonactivated fibroblasts are differentially affected by short-term exposures to 5FU or MMC. These findings may have important clinical implications regarding the concentrations of these agents used in the treatment of different patient groups.